Rapid and preferential distribution of blood-borne αCD3εAb to the liver is followed by local stimulation of T cells and natural killer T cells

Gerhard Wingender, Beatrix Schumak, Anna Schurich, J. Engelbert Gessner, Elmar Endl, Andreas Limmer, Percy A. Knolle

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Dissemination of soluble molecules or antigens via the blood stream is considered to lead to a uniform distribution in the various organs of the bodyq4, but organ-specific microarchitecture and vascularization may influence this. Following intravenous injection of αCD3ε antibody q5(αCD3εAb) we observed clear differences in antibody binding to Fcγ receptor (FcγR)+ antigen-presenting cells (APCs) or T lymphocytes in different organs. Significant binding of blood-borne αCD3εAb was only detected in the spleen and liver and not in the thymus or lymph node. In the spleen, only 10% of dendritic cells/macrophages and 40% of T-cell receptor (TCR)-β+ cells were positive for αCD3εAb, and, dependent on FcγR-mediated cross-linking of αCD3εAb, a similar percentage of splenic TCR-β+ cells were stimulated and became CD69+. Stimulation of TCR-β+ cells in the liver was at least as efficient as in the spleen, but almost all T cells and all scavenger liver sinusoidal endothelial cells bound αCD3εAb. In contrast to CD69 up-regulation, only CD4 + natural killer T (NKT) cells and CD11ahigh CD8 + T cells were activated by αCD3εAb and expressed interferon (IFN)-γ. Again, IFN-γ release from NKT/T cells was at least as efficient in the liver as in the spleen. Taken together, our results support the notion that the combination of extensive hepatic vascularization and very high scavenger activity allows the liver to fulfill its metabolic tasks and to promote stimulation of the large but widely distributed hepatic population of NKT/T cells.

Original languageEnglish
Pages (from-to)117-126
Number of pages10
JournalImmunology
Volume117
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

Keywords

  • Fcγ receptor
  • Innate immunity
  • Liver sinusoidal endothelial cells
  • Natural killer T cells

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